The objective of this proposal is to determine the pathophysiological role of circulating cardiodepressant substances in the genesis of terminal cardiovascular collapse in shock states. The long-term goals of this project include the isolation, identification and characterization of the shock induced substances which exert cardiodepressant activity. Furthermore, this project seeks to determine the pathophysiological role of these shock substances via the selective removal of these substances from the circulation during shock states. Results to date indicate that there may be more than one cardiodepressant substance in shock serum. Initial isolation studies on low molecular weight compounds revealed that L-leucine could exert cardiodepressant action and was isolated from shock serum. In vivo measurements of plasma leucine in shocked rats and dogs disclosed that leucine concentrations increased as the shock state progressed. Additionally, the infusion of leucine into shocked rats hastened their deaths compared to control shocked rats. These data indicate that excess plasma leucine may accelerate terminal cardiovascular collapse in shock states.